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Biomarkers of Immune Activation in African Americans with CKD

患有 CKD 的非裔美国人免疫激活的生物标志物

基本信息

批准号：
10397070
负责人：
Teresa Chen
金额：
$ 3.64万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10397070
关键词：
APOL1 gene Adaptive Immune System Affect African American African American population African ancestry American Amlodipine Applications Grants Atherosclerosis Risk in Communities Award Biological Markers Biology Blood Pressure Chronic Kidney Failure Chronic Kidney Insufficiency Clinical Complex Data Data Analyses Data Store Development Dietary Factors Dietary Potassium Dietary Sodium Disease Progression Doctor of Philosophy End stage renal failure Endothelial Cells Ensure Environment Epidemiology European Experimental Models Funding Mechanisms Future General Population Genotype Goals High Prevalence Hour Human body Hypertension Immune Immunologic Markers In Vitro Individual Intake Interferon Type II Intervention Invaded Investigation K-Series Research Career Programs Kidney Diseases Letters Link Measurement Measures Mentors Mentorship Methods Metoprolol Molecular Epidemiology Nephrology Outcome Oxidative Stress Pathway interactions Pharmaceutical Preparations Phase Populations at Risk Potassium Ramipril Randomized Renal function Reproducibility Research Research Design Research Personnel Research Project Grants Resources Risk Risk Factors Role Sampling Scientist Serum Sodium Sodium Chloride System TNF gene Time Training Tryptophan Metabolism Pathway Tumor Necrosis Factor Activation Tumor Necrosis Factor Receptor United States National Institutes of Health Universities Urine Visit Water blood pressure control blood pressure intervention blood pressure medication career cohort demographics diabetic patient endothelial dysfunction experience fatty acid oxidation follow-up genetic epidemiology genetic risk factor high risk immune activation improved insight medical schools metabolomics microorganism non-diabetic novel podocyte predictive marker professor randomized trial receptor risk variant skills treatment arm trial design

项目摘要

PROJECT SUMMARY/ABSTRACT Teresa K. Chen, MD, MHS is an Assistant Professor in the Division of Nephrology at Johns Hopkins University School of Medicine. She is applying for a K08 Mentored Clinical Scientist Research Career Development Award in order to acquire the necessary skills and mentored research experience to become an independent investigator in the field of chronic kidney disease (CKD). The proposed 5-year plan includes advanced coursework in epidemiology; practical experience in the measurement of biomarkers; and mentorship by an extraordinarily experienced, committed and diverse mentorship team [co-primary mentors, Lawrence Appel, MD, MPH and Morgan Grams, MD, PhD; co-mentor, Michelle Estrella, MD, MHS]. With resources provided by this award, Dr. Chen will develop proficiencies in study design, genetic and molecular epidemiology, and longitudinal data analysis related to CKD. Her proposed research project focuses on the role of immune activation in CKD progression and the interactive effects of immune activation with APOL1 risk variants. African Americans are disproportionately affected by CKD. This is in part due to the higher prevalence of APOL1 risk variants, genetic risk factors for kidney disease among individuals of African ancestry. The role of immune activation in the progression of non-diabetic CKD, particularly in APOL1 high-risk individuals, is unclear. The objectives of the proposed research are to: 1) study the associations of biomarkers of immune activation with CKD progression among non-diabetic African Americans with CKD attributed to hypertension; 2) determine whether the APOL1-associated risk for CKD progression is augmented by immune activation; 3) assess whether blood pressure interventions and dietary factors are associated with longitudinal changes in biomarkers of immune activation; 4) identify metabolomic predictors of biomarkers of immune activation. With over 10 years of follow-up, rigorously collected data, and stored biospecimens, the African American Study of Kidney Disease and Hypertension (AASK) represents an ideal cohort in which to study these potential associations. APOL1 genotyping and metabolomics measurements have previously been completed in AASK through other NIH-funded mechanisms. We propose to use stored serum samples from the baseline and 12- month visits of the trial phase to measure the following biomarkers of immune activation: tumor necrosis factor alpha (TNF-α), soluble TNF receptors 1 and 2 (sTNFR1 and sTNFR2), and interferon gamma (IFN-γ). The results of the proposed study will clarify the role of immune activation in CKD progression and perhaps identify novel targets for intervention. This could have important clinical implications in the treatment of African Americans with non-diabetic CKD, particularly among those with the APOL1 risk variants. The proposed research will also support Dr. Chen's long term-goal of transitioning towards an independent research career that ultimately improves the management and outcomes of African Americans with CKD. The rich training environment of Johns Hopkins University will ensure that she achieves these goals.

项目总结/文摘